Table 2.

Pharmacological properties of phillyrin and possible mechanisms.

Models	Mechanism	Reference
Effects on metabolic disorders
Mice fed with HFD	Phillyrin lowered body weight via the modulation of PPARβ/δ–ANGPTL 4 signaling pathway.	[20]
3T3-L1 adipocytes	Phillyrin promoted glucose uptake in insulin resistance 3T3-L1 adipocyte through activation of PI3K/Akt signaling pathway.	[21]
Rats fed with HFD	Not available	[22]
Anti-inflammatory effects
Mouse model of traumatic brain injury	Phillyrin activated PPARγ signaling pathway to inhibit phosphorylation of NF-κB and its downstream pro-inflammatory action in microglia.	[23]
Mouse model of acute kidney injury induced by LPS	Phillyrin inhibited the activation of the NF-κB and MAPK signaling pathway, decreasing the levels of inflammatory cytokines (TNF-α, IL-1β, IL-6).	[24]
Lethal LPS-induced neutrophil Inflammation in zebrafish	Phillyrin reduced neutrophil infiltration, necrosis and inflammation via suppression of MyD88–NF-κB signaling pathway.	[25]
LPS-treated RAW264.7 cells; LPS-induced acute lung injury	Phillyrin inhibited the secretion of IL-6 and NO in RAW264.7 cells via TLR4 signaling pathway.	[26]
LPS-treated BV2 microglia cells	Phillyrin downregulated the expression of TLR4.	[27]
Periodontitis rats	Phillyrin reduced the phosphorylation of p38 MAPK and the expression of c-Fos.	[28]
LPS-treated mouse mammary epithelial cells	Phillyrin may decrease the secretion of inflammatory cytokines via inhibition of TLR4/MyD88/Traf-6/NIK or the TLR4/MyD88/Traf-6/IκB pathway.	[29]
LPS-treated rat hepatic stellate cells	Phillyrin restrained the expression of phosphorylated NF-κB p65 protein to inhibit HSC-T6 activation.	[30]
THP-1 cells stimulated with Staphylococcus aureus in vitro	Phillyrin inhibited the expression of TLR2 and TRL4.	[31]
Atherosclerosis in SD rats	Phillyrin reduced oxidative stress via decreasing gene and protein expression of NHE-1.	[32]
Traumatic fracture in SD rats	Phillyrin reduced the serum levels of inflammatory factors such as iNOS, TNF-α and IL-6.	[33]
Anti-aging effect
Mouse model of aging induced by D-galactose	Phillyrin enhanced the activity of SOD and decreased the activity of MAO-B to improve the ability of scavenging free radicals in mice to inhibit aging.	[34]
Antiviral effect
Mice infected with influenza A virus	Phillyrin may reduce inflammation induced by influenza A virus and inhibit viral replication.	[35]
Antibacterial effect
Caenorhabditis elegans–Pseudomonas aeruginosa infection model	Phillyrin possibly suppress pathogen virulence factors to protect Caenorhabditis elegans from Pseudomonas aeruginosa.	[36]
Klebsiella pneumonia (Kp) infected mice	Phillyrin activated STAT5/Foxp3 pathway in Kp infected mice to promote the balance of Th17/Treg cells and relieving the disease.	[37]
Wound surface of rats with perianal abscess	Phillyrin reduced the number of Escherichia coli in the wound of perianal abscess rats by activating JAK2/STAT3 pathway.	[38]
Hepatoprotective effects
Mouse model of liver fibrosis	Phillyrin inhibited NF-κB and TGF-β1/Smad2/3 signal pathway to repress the inflammatory response of macrophages and the activation of hepatic stellate.	[39]
Human liver cell line LO2 treated with alcohol	Phillyrin inhibited the expression of apoptosis related proteins PARP and Caspase 3.	[40]
Nephroprotective effects
Diabetic nephropathy in rats induced by HFD and streptozotocin	Phillyrin inhibited inflammation and alleviated renal injury associated with depressed TGF-β1 expression.	[41]
Diabetic nephropathy in mice induced by streptozotocin	Phillyrin suppressed renal cell apoptosis via activation of PI3K/Akt/GSK-3β signaling pathway in kidney.	[42]
Anti-cancer effects
Lewis lung carcinoma mice	Phillyrin inhibited lung tumor development by downregulating VEGF expression and upregulating endostatin expression, respectively.	[43]
HEp-2 cells	Phillyrin-induced autophagy may be through the AMPK/mTOR/p70S6K signaling pathway.	[44]